Engineering Sequence-Defined Macromolecules for Drug Delivery and Plastics
Precise sequence and structural control is critical to the development of new functional, responsive and programmable materials. Motivated by these opportunities and the need for sequence-control and structural diversity in synthetic polymer research, I will present two versatile strategies for the assembly of sequence-defined macromolecules. In the first strategy, I will discuss our work on the design and assembly of oligothioetheramides (OligoTEAs). As new macromolecular class, oligoTEAs are uniquely suited to design and create therapeutic drugs and delivery scaffolds due to their rapid synthetic assembly with precise sequence-control and a large collection of chemically diverse monomers. Moreover, their abiotic backbone renders them resistant to proteolysis, which is beneficial for a wide range of biological applications. My group has investigated and used this versatile synthetic macromolecular platform to i) create well-defined and potent antimicrobial compounds, ii) create intracellular target specific probes for measuring intracellular bond cleavage rates, iii) create sequence-specific antibody-drug conjugates, and iv) create cell-penetrating oligomers. In this talk, I will focus on the use of oligoTEAs to design a new class of non-charged cell-penetrating macromolecules for antibiotic delivery. In the second strategy, I will present new synthetic platform that overcomes the scalability issue that plagues the iterative assembly of sequence-defined macromolecules. This method facilitates the assembly of sequence-defined polyurethane macromers at the gram-scale. Data highlighting the effect of sequence on network topology and mechanical properties will be discussed. Overall, this body of work should provide the foundation for future studies exploring the tunability of bulk material properties via sequence control.